Genes Up- or Down-regulated by High Calcium Medium in Parathyroid Tissue Explants from Patients with Primary Hyperparathyroidism

Abstract

To investigate genes modulated in the parathyroid glands by calcium, expression levels of mRNA for all genes expressed in parathyroid tissue explants (PTEs) obtained from patients with primary hyperparathyroidism (I°-HPT) were analyzed by oligo-DNA microarray. PTEs obtained from 4 patients with I°-HPT were precultured in normocalcemic medium (Ca⁺⁺ 1.0-1.1 mM) for 7 days and then cultured in hypocalcemic medium (Ca⁺⁺ 0.60 mM) or hypercalcemic (Ca⁺⁺ 1.60 mM) medium containing 4mg/dl phosphate for an additional 7 days. As expected, expression levels of mRNA for PTH and chromogranin A were decreased to less than 50% in the hypercalcemic medium when compared with those in the hypocalcemic medium. Furthermore, oligo-DNA microarray analyses revealed that 7 genes were up-regulated by more than 2-fold and more than 30 genes were down-regulated by more than 1/2 in PTEs. Interestingly, 9 of these genes (up-regulated genes: chemokine ligand 8, multiple C2 domain and transmembrane region protein 1; down-regulated genes: matrix metallopeptidase-9, B-box and SPRY domain-containing protein, nitric oxide synthase 2A, PTH, cartilage acidic protein 1, chromogranin A, and fibrin 1) were involved in calcium metabolism or calcium-signaling pathways in the parathyroid tissue. However, the expression level of mRNA for α-klotho was variable, and it was not constantly decreased in hypercalcemic medium under the present experimental conditions. Although it was not possible to use normal parathyroid tissue, this is the first reported study to have investigated the expression levels of mRNA for all genes in human parathyroid adenomas that are modulated by high calcium concentration in organ culture.